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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
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Androgen Receptor Signaling in Castration-Resistant Prostate Cancer Alters Hyperpolarized Pyruvate to Lactate
Niki Zacharias1,2,3, Jaehyuk Lee1, Sumankalai Ramachandran4
1Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1881 East Road, Unit 1907, Houston, TX, 77054, USA.
Molecular Imaging and Biology
|May 12, 2018
Summary
Castration-resistant prostate cancer (CRPC) subtypes show distinct metabolic profiles. AR-dependent CRPC exhibits increased lactate production, unlike aggressive variant prostate cancer (AVPC), suggesting metabolic imaging can differentiate CRPC subtypes.
Area of Science:
- Oncology
- Metabolic Imaging
- Prostate Cancer Research
Background:
- Androgen receptor (AR) signaling drives prostate cancer (PCa) progression, often leading to castration-resistant prostate cancer (CRPC) after therapy.
- CRPC is broadly classified into AR-dependent and aggressive variant prostate cancer (AVPC) subtypes, each with distinct molecular and phenotypic characteristics.
- Patient-derived xenograft (PDX) models recapitulate CRPC subtypes, offering valuable tools for studying their biology.
Purpose of the Study:
- To investigate metabolic alterations in AR-dependent CRPC and AVPC subtypes using PDX models.
- To assess the utility of hyperpolarized 1-[13C]pyruvate spectroscopy for in vivo phenotyping of CRPC.
Main Methods:
- Utilized prostate cancer PDX models representing AR-dependent CRPC and AVPC subtypes.
- Employed mass spectrometry, nuclear magnetic resonance, and in vivo hyperpolarized 1-[13C]pyruvate spectroscopy.
- Measured 1-[13C]pyruvate conversion to 1-[13C]lactate in vivo and ex vivo.
Main Results:
- AR-dependent CRPC PDX models demonstrated significantly increased lactate production compared to AR-negative AVPC PDX models.
- Elevated lactate production in AR-dependent CRPC was observed even under low-hormone conditions.
- Hyperpolarized 1-[13C]pyruvate spectroscopy effectively detected metabolic differences between CRPC subtypes.
Conclusions:
- Metabolic differences, specifically lactate production, can distinguish between AR-dependent CRPC and AVPC subtypes.
- Hyperpolarized metabolic imaging holds promise for in vivo phenotyping and understanding the underlying biology of CRPC.
- This approach may aid in personalized treatment strategies for advanced prostate cancer.
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